IL-18 and infections: Is there a role for targeted therapies?

Abstract:

:Interleukin (IL)-18 is a pro-inflammatory cytokine belonging to the IL-1 family, first identified for its interferon-γ-inducing properties. IL-18 regulates both T helper (Th) 1 and Th2 responses. It acts synergistically with IL-12 in the Th1 paradigm, whereas with IL-2 and without IL-12 it can induce Th2 cytokine production from cluster of differentation (CD)4+ T cells, natural killer (NK cells, NKT cells, as well as from Th1 cells. IL-18 also plays a role in the hemophagocytic lymphohistiocytosis, a life-threatening condition characterized by a cytokine storm that can be secondary to infections. IL-18-mediated inflammation was largely studied in animal models of bacterial, viral, parasitic, and fungal infections. These studies highlight the contribution of either IL-18 overproduction by the host or overresponsiveness of the host to IL-18 causing an exaggerated inflammatory burden and leading to tissue injury. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the coronavirus disease 2019 (COVID-19). The damage in the later phase of the disease appears to be driven by a cytokine storm, including interleukin IL-1 family members and secondary cytokines like IL-6. IL-18 may participate in this hyperinflammation, as it was previously found to be able to cause injury in the lung tissue of infected animals. IL-18 blockade has become an appealing therapeutic target and has been tested in some IL-18-mediated rheumatic diseases and infantile-onset macrophage activation syndrome. Given its role in regulating the immune response to infections, IL-18 blockade might represent a therapeutic option for COVID-19, although further studies are warranted to investigate more in detail the exact role of IL-18 in SARS-CoV-2 infection.

journal_name

J Cell Physiol

authors

Vecchié A,Bonaventura A,Toldo S,Dagna L,Dinarello CA,Abbate A

doi

10.1002/jcp.30008

subject

Has Abstract

pub_date

2021-03-01 00:00:00

pages

1638-1657

issue

3

eissn

0021-9541

issn

1097-4652

journal_volume

236

pub_type

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